The aim of this project is to determine the role of abnormal lymphokine/cytokine expression in the immunopathogenesis of common variable immunodeficiency (CVI) and other immunodeficiency states. During the present period we studied the immunologic properties of an unusual CD8+/HLA-DR+ T cell subset that is abnormally expanded in a subgroup of patients with CVI. These CD8+ T cells produced significantly less EL-2 and more gamma-interferon than did normal CD8+ T cells. In contrast, patient CD8+ T cells were found to secrete normal amounts of EL-4, IL-5, and GM-CSF. This abnormal pattern of lymphokine expression was limited to CD8+ T cells, as purified CD4+ T cells from these patients exhibited a normal pattern of lymphokine expression. In addition, the abnormal CD8+ T cell lymphokine secretion pattern was associated with a functional defect: patient T cells were more potent at suppressing Ig production by normal B cells than were CD8+ T cell from normal controls. Finally, when purified CD8+ T cells from CVI patients with a normal CD4/CD8 ratio were examined, they were found to exhibit normal IL-2 and gamma-interferon production. Thus, the expanded population of CD8+ T cells in this subgroup of patients exhibit an unusual pattern of lymphokine secretion that appears to define a distinct subset of patients with CVI. In related studies we identified a patient with a novel lymphoproliferative disorder of TCRAlpha/Beta CD4-CD8- T cells. The clinical and immunological features of this case closely resemble the lymphoproliferative/autoimmune disease seen in lpr and gld mice. The large percentage of TCRAlpha/Beta CD4-CD8- T cells in this patient's peripheral blood allowed us to isolate these cells and characterize their phenotypic and functional properties. These studies define the clinical and immunological characteristics of a new disease entity.